1. Field of Invention
The invention comprises the use of electromagnetic energy to make physical and biochemical alterations to the ocular lens of a mammalian eye for the correction of visual impairments, particularly presbyopia and including other ametropias such as myopia, hyperopia and regular and irregular astigmatism, and the retardation of cataract development.
2. Description of Related Art
Vision impairment is an exceedingly common problem in humans. Nearly 100% of people over age 50 have some form of vision impairment. The need for corrected vision (e.g., the need for glasses or contacts) is also very common among younger people. In a vast majority of people needing vision correction the problem is associated with the crystalline lens of the eye. Two primary problems that occur in the crystalline lens are (a) insufficient flexibility resulting in the inability to correctly focus incoming light and (b) light scattering also resulting in blurred vision.
The common errors of focusing of the eye fall into a class of visual impairments termed ametropias, which include myopia, hyperopia, astigmatism (regular and irregular) and presbyopia. These impairments generally cause visual blurring, and are most commonly corrected with eyeglasses or contact lenses, and sometimes with surgery. Myopia is the ocular condition where light from a distant object focuses in front of the retina resulting in blurred distance vision, while visual images of near objects are generally clear. Myopia is the most common reason for vision correction in a population under age 30. In hyperopia, an image of a distant object is focused behind the retina, making distance and near vision blurred, except where described later. Hyperopia, although exceedingly common, is not normally corrected until the fortieth decade when presbyopia makes correction necessary. Astigmatism is a refractive error that results in the eye's inability to focus along a first axis in a plane perpendicular to the line of sight being different from the eye's ability to focus along a second axis in the same plane perpendicular to the first axis, thus producing an image incapable of focusing at any distance. Astigmatism generally occurs as a second impairment along with either myopia or hyperopia, but is occasionally the only reason for needing visual correction. Astigmatism is subdivided by type and includes regular and irregular astigmatism as well as aberration. In irregular astigmatism there are other distortions or aberrations which are in some persons corrected by considering its effect upon the wavefront function. The wavefront function characterizes the refractive profile of the eye and defines irregular astigmatism, which is considered a higher order optical aberration such as spherical aberration, coma, trifoil, and others often characterized by Zernicke polynomials above the fourth order. (See, for example, Rae, Krueger & Applegate, Customized Corneal Ablation (2001), which is specifically incorporated herein by reference).
Of the ametropias, presbyopia stands out as a significant problem because of its prevalence and because it is not corrected as successfully as are myopia and hyperopia with the current treatment methods. Presbyopia is the focusing error caused by a loss of flexibility of the ocular lens. Lens flexibility allows for accommodation, which is the primary mechanism by which the eye changes focus. Accommodation is the change in shape of the ocular lens as it responds to neural feedback, ideally to focus light precisely on the back of the retina, allowing the perceived image to be seen in sharp focus. Presbyopia generally causes clinically significant blurred vision in humans starting between the ages of 40 and 50 years, and is one of the few human disorders with a prevalence of 100% in the population that reaches the age of the mid-50's.
Functionally, loss of accommodation is a life long process through which the ability of the ocular lens to change shape to allow for focused vision continually decreases starting essentially at birth. This change is evidenced in the following typical data comparing the eye's focusing ability, here measured by the eye's shortest focal length in units of diopters (the reciprocal of focal length measured in meters) to the age of an eye: 14 D. (focal length at 7 cm) at 10 years; 8.00 D. (f=12.5 cm) at 30 years, 4.00 D. (f=25 cm) at 45 years, and 1.00 D. (f=100 cm) at 52 years.
Until absolute presbyopia (i.e., no accommodation) occurs, focusing on close objects is achieved through the control of the ciliary muscle. Two theories of how this occurs have coexisted for more than 100 years, and have only recently been clarified by direct observation with sophisticated cameras and ultrasound systems. The Helmholz theory first proposed in 1909 basically defines the crystalline lens as being held in resting tension by the ciliary muscle when the lens is focused for a distance object. When the lens focuses on nearer objects, it is through the relaxation of the ciliary muscle, and releasing of any tension on the lens, yielding a thicker or more convex lens.
In addition to presbyopia, it is well known that another process occurs within the ocular lens throughout a normal human life that also generally becomes clinically diagnosable during the fourth decade of life. This second degenerative process manifests as the scattering of light as it passes through the lens. The process that leads to light scattering is the first step to cataract development.
Cataracts are areas of opacification of the ocular lens of sufficient size to interfere with vision. They have been extensively studied because of their high prevalence in a geriatric population. Cataracts in the aged (senile cataracts) are the most common type, and are often thought to be due to an acceleration of the previously mentioned light scatter. Cataracts occur to varying extents in all humans over the age of 50 years, but generally do not cause significant visual dysfunction until the ages of 60-80 years. Cataracts, however, can occur much earlier as a result of risk factors including disease, trauma, and family history.
FIG. 2 is presented as an aid to understanding the visual impairments related to the ocular lens (3). The ocular lens (3) is a multi-structural system as illustrated in FIG. 2. The macroscopic lens structure includes a cortex (13) just inside a capsule (14), which is an outer membrane that envelopes the other interior structures of the lens. The nuclei are formed from successive additions of the cortex (13) to the nuclear regions, which are subdivided into a deep fetal nucleus (22), which develops in the womb, an infantile nucleus (24), a juvenile nucleus (26), and the adult nucleus (28). On the microscopic level the structure of the nuclei is layered, resembling the structure of an onion with the oldest layers and oldest cells towards the center. Rather than being spherical, the lens is a biconvex shape as shown in FIG. 2. The cortex and the different nuclei have specific structures that are consistent through different ages for specific cell sizes, compactions, and clarity. The lens epithelium (23) forms at the lens equatorial region (21) generating ribbon-like cells or fibrils that grow anteriorly and posteriorly around the ocular lens. The unique formation of the crystalline lens is the biconvex shape where the ends of the cells align to form a suture in the central and paracentral areas both anteriorly and posteriorly. Transparency is maintained by the regular architecture of the fibrils. As long as the regular architecture is maintained, light passes unobstructed through the lens. The older tissue in both the cortex and nucleus has reduced cellular function, having lost their cell nuclei and other organelles several months after cell formation. The aqueous (17), the liquid in the anterior chamber between the lens and cornea flows very slowly through the lens capsule (14) and the sutures into more remote areas of the lens and provides the nutrients needed for minimal cellular life functions, including the removal of toxic and oxidative byproducts.
The microstructure of the fibrils contains interconnections between the ribbon-like fibrils called balls and sockets and interdigitations and imprints, which to some extent inhibit the relative motion of fibrils with respect to one another. Still, the fibrils are relatively free to move in relation to each other in the young, flexible crystalline lens. As the eye ages, there are age related changes to these structures that include the development of intermolecular bonding, mostly disulfide bonding, the compaction of tissue, the breakdown of some of the original attachments, and the yellowing or darkening of older lens areas.
Changes in the size and shape of the macroscopic lens components throughout life include both the increased curvature and general enlargement of the biconvex lens with age. The thickness of the posterior portion increases more than the anterior portion. Additionally, thickness increases are proportionately greater in the periphery.
The above mentioned disulfide bonding immobilizes the oldest and deepest lens tissue, characteristically seen in the nuclear regions. However, disulfide bonds are weak chemical bonds, and are subject to modification and breakage with relatively little energy. The disulfide bonds are largely formed by the effects of ambient ultraviolet (UV) light from the atmosphere and from the continual, unrelenting reduction in lens movement with age (presbyopia). The lens absorbs fluids from the aqueous, a process enhanced by lens accommodation, e.g., the undulating movement of the younger crystalline lens. The aqueous normally contains antioxidants that aid in preventing disulfide bond formation that further inhibits lens movement.
Just as for the mechanism of presbyopia, light scattering and cataractogenesis results from interfibril attachment. On the cellular level, all cataracts begin with oxidative changes of the crystalline tissue. The changes in the lens tissue that lead to light scattering occur when individual fibers combine to form large, light-disrupting macromolecular complexes.
The two different processes that lead to presbyopia and light scattering occur simultaneously and continuously but at different rates. The possible connection between the two processes was clarified by a 1994 report by Koretz et al. (Invest. Ophthal. Vis. Science (1994)), the entirety of which is specifically incorporated herein by reference to the extent not inconsistent with the disclosures of this patent. Koretz et al. studied extensively the presence of zones of light scatter. They not only confirmed that older lenses had more light scatter, but also they reported an acceleration in the rate of formation of light-scattering macromolecular complexes starting in the fourth decade of life. Since certain natural antioxidants within the lens are known to counteract the changes that produce light scatter, Koretz theorized that reduced lens movement due to decreased accommodation reduces the flow of fluids carrying the antioxidants and thereby exacerbates the process leading to light scattering.
As further foundation for this discussion, the anatomical structures of the eye are shown in FIG. 1, a cross sectional view of the eye. The sclera (31) is the white tissue that surrounds the lens except at the cornea. The cornea (1) is the transparent tissue that comprises the exterior surface of the eye through which light first enters the eye. The iris (2) is a colored, contractible membrane that controls the amount of light entering the eye by changing the size of the circular aperture at its center (the pupil). The ocular or crystalline lens (3), a more detailed picture of which is shown in FIG. 2, is located just posterior to the iris. Generally the ocular lens changes shape through the action of the ciliary muscle (8) to allow for focusing of a visual image. A neural feedback mechanism from the brain allows the ciliary muscle (8), acting through the attachment of the zonules (11), to change the shape of the ocular lens. Generally, sight occurs when light enters the eye through the cornea (1) and pupil, then proceeds past the ocular lens (3) through the vitreous (10) along the visual axis (4), strikes the retina (5) at the back of the eye, forming an image at the macula (6) that is transferred by the optic nerve (7) to the brain. The space between the cornea and the retina is filled with a liquid called the aqueous in the anterior chamber (9) and the vitreous (10), a gel-like, clear substance posterior to the lens.
The traditional solution for the correction of presbyopia and other refractive errors is to provide distance glasses, reading glasses, or a combination of the two called bifocals. Other forms of correction include the following: a) variable focus bifocal or progressive spectacles, b) contact lenses, c) aspheric corneal refractive surgery, and d) intraocular implant lenses for aphakic (absence of the ocular lens) individuals. Bifocal contact lenses are uncommonly used because, for fitting or for technical reasons, they are optically inferior to bifocal spectacles. An additional corrective method using contact lenses called “monovision” corrects one eye for near and the other for far, and the wearer learns to alternate using each eye with both open. Aspheric photorefractive keratectomy (such as is described in Ruiz, U.S. Pat. No. 5,533,997 and King, U.S. Pat. No. 5,395,356, the entire disclosures of which are specifically incorporated herein by reference to the extent not inconsistent with the disclosures of this patent) provides variable focus capabilities through an aspheric reshaping of the cornea. Similar to this optical correction, some aspherical intraocular implant lenses take the place of the natural ocular lens in individuals whose lens has been removed during cataract surgery. All of these techniques have one or more of the following disadvantages: a) they do not have the continuous range of focusing that natural accommodation provides; b) they are external devices placed on the face or eye; or c) they cut down the amount of light that normally focuses in the eye for any one particular distance, a particular problem because middle-aged individuals actually need more light because of light loss due to the development of light scattering, as described above.
Further treatments founded on using nutritional supplements have been considered to enhance accommodation and retard cataract development. Additionally, behavioral optometrists proposed many years ago the use of focusing exercises to slow down the deterioration of lens accommodation. None of these treatments has been widely accepted.
Alternative treatment methods to glasses have been more successful in correcting such refractive errors as myopia (nearsightedness), hyperopia (farsightedness), and astigmatism compared with their limited success in treating presbyopia. Such alternative treatments use photorefractive procedures in an attempt to correct refractive errors and avoid the necessity of external lenses (e.g., spectacles and contact lenses), including the currently FDA-approved procedures of photorefractive keratectomy (PRK) and laser-assisted keratomileusis (LASIK). PRK and LASIK treatments use a laser to produce a unique shape in the static cornea of the eye that is calculated to precisely focus light at the retina taking into account the dimensions and limitations of other structures of the eye, especially the crystalline lens. These procedures are of limited utility specifically because they treat the static cornea and do not account for the dynamics of the crystalline lens, which change over time as evidenced by the occurrence of presbyopia.
Another disadvantage of the present photorefractive procedures is that they generally involve fairly invasive surgery. For instance, LASIK requires an incision in the cornea to create a flap of tissue that is peeled back to expose the interior of the cornea, which is then precisely sculpted to focus light on the retina.
For presbyopic correction specifically, current methods generally require surgical incision and physical penetration of a portion of the eye. For instance, Werblin (U.S. Pat. No. 5,222,981) proposed the surgical removal of the clear, intact crystalline lens for the purpose of correcting presbyopia and other ametropias, and substituting a multiple interchangeable components-intraocular lens. Removal of the lens requires an incision through which it can be removed.
Another development in photorefractive treatment of presbyopia is Bille (U.S. Pat. No. 4,907,586), which primarily describes a quasi-continuous laser reshaping the eye, namely the cornea and secondarily the crystalline lens in order to correct myopia, hyperopia, and astigmatism. Bille, however, also proposed that presbyopia might be corrected by semi-liquification or evaporation of lens tissue through treatment with a quasi-continuous laser.
In WO95/04509 and again later in U.S. Pat. No. 6,322,556, Gwon described a method to correct presbyopia, myopia, and hyperopia with an ultrashort laser pulse that produced volumetric reductions of lens tissue. While various methods to replace the clear crystalline lens with a flexible or gel intraocular implant have been developed as an alternate lenticular technology, Gwon's patented method was the only major milestone in direct treatment of the natural lens.
Scleral expansion is a presbyopia treatment method proposed in patents by Schachar (U.S. Pat. Nos. 5,529,076, 5,503,165, 5,489,299, and 5,465,737). In these patents, Schachar discloses a method of stretching the sclera, which restores accommodation by shifting the attachment of the cilliary muscle, allowing the lens to stretch its diameter. In addition, he suggests an alternative embodiment involving the use of laser irradiation of the lens to destroy the germinal epithelium to remove the source of growth of the crystalline lens. Schachar's method has been described to work according to the Tscherning mechanism, an alternative mechanism to the Helmholz theory and is an example of the multiplicity of presbyopia theories present in the field through the late 1990s.
Development of crystalline lens modification technology and presbyopia correction specifically may have been slow after 1990 because the Bille patent was directed (as was other research in the field) primarily toward the cornea, a simpler system than the dynamic crystalline lens because it a static refractive surface.
Another reason that crystallin lens modification technology has developed slowly is that ophthalmic professionals are accustomed to wholly removing the crystalline lens during cataract surgery, the most commonly performed surgery in the United States (greater than one million per year). Modifying the crystalline lens is considered the antithesis of the prevailing thought about lens removal. Also, ophthalmic professionals have traditionally looked upon the crystalline lens as susceptible to cataract development from a wide variety of causes especially trauma such as that of surgery directly on this tissue. A summary consisting of sixty-nine pages in Davson's The Eye (1980), illustrates the wide breadth of causes of cataracts in the crystalline lens, including ultraviolet, infrared, and ultrasound energy; incisional surgery from the anterior (e.g., cornea) or the posterior (e.g., retina); many systemic diseases including diabetic changes from hyper- to hypo-glycemic conditions; trauma; toxic chemicals and pharmacological drugs; and malnutrition and vitamin deficiencies.
A reason that laser surgery is of particular interest is that much of the ocular media is transparent to the visible light spectrum, i.e., wavelengths of 400-700 nanometers (nm); thus, light of wavelengths in this range pass through the anterior eye without effect. While the near-visible spectrum on either side of the visible range, including ultraviolet and infrared light, has certain absorptive characteristics in various ocular tissues and may cause changes in the tissue, the safety of light irradiation can be specified according to a threshold energy level below which particular tissues will not be adversely affected. Above the threshold, ultraviolet or infrared light can cause damage to the eye, including the establishment of cataracts or even tissue destruction. The ability to destroy ocular tissue, however, can be made to be quite beneficial, and is a major premise underlying eye surgeries using light energy. As described below, light energy can be focused to a specific point, where the energy level at that point (expressed as a energy density) is at or above the threshold for tissue destruction. Energy in the light beam prior to focusing can be maintained at a energy density below the threshold for tissue destruction. This “pre-focused” light can be referred to using the term subthreshold bundles (described by L'Esperance, U.S. Pat. No. 4,538,608, the entire disclosure of which is specifically incorporated herein by reference to the extent not inconsistent with the disclosures of this patent), wherein the “bundles” are not destructive to tissue.
Lasers have been used widely to correct many ocular pathological conditions, including the suppression of hemorrhaging, the repair of retinal detachments, the correction of abnormal growth of the lens capsule after cataract surgery (posterior capsulotomy), and the reduction in intraocular pressure. Therefore, various laser sources providing numerous and even continuously variable wavelengths of laser light are well know in the art. The characteristics of the laser, including its wavelength and pulsewidth make different types of lasers valuable for specific purposes. For example, an excimer laser with pulsed UV light of 193 nm has been selected for photorefractive keratectomy (PRK) because it yields an ablation with very little heat release, and because it treats the corneal surface without penetrating the cornea. There are other excimer lasers that use wavelengths from 300-350 nm that will pass through the cornea and into the lens.
High energy light having a wavelength in the range from 100-3000 nm can be produced by various types of laser sources, including those using gases to produce the laser energy, such as the KrF excimer laser; solid state lasers, such as the Nd-YAG and Nd-YLF laser; and tunable dye lasers. No matter the laser source, the physical and chemical effects of coherent light from a laser upon ocular tissue vary according to a number of laser parameters, including wavelength, energy, energy density, focal point size, and frequency. Photodisruption and photoablation describe laser-tissue interactions in which some tissue is destroyed. The term photoablation has been used to describe tissue destruction for photorefractive keratectomy using an excimer laser, as well as for tissue destruction using infrared lasers. Within this application, the term photodisruption is used as described below in the Detailed Description, and may be used herein similarly to uses of the term photoablation in other references.
Of the various sources, infrared nanosecond and picosecond pulsed lasers such as the Nd-YAG and Nd-YLF have been used on the lens because they can focus for treatment deep in a transparent system, and because they remove tissue with minimal effect upon adjacent tissues. The size of the initial tissue destruction using these lasers is relatively large, however. New generation infrared lasers performing in the femtosecond range (10−15 seconds) can produce a smaller tissue disruption. (See Lin, U.S. Pat. No. 5,520,679).